早期美托洛尔治疗对急性心肌梗死大鼠心肌炎症因子表达和心功能的影响  

Effects of early treatment with metoprolol on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction

作　　者：程翔[1] 廖玉华[1] 李彬[1] 杨亚利[1] 张金盈[1] 逯保军[1] 葛洪霞[1] 刘英[1] 郭张强[1] 张玲[1] 

机构地区：[1]华中科技大学同济医学院心血管病研究所协和医院心内科心血管免疫实验室,武汉430022

出　　处：《中华心血管病杂志》2005年第5期448-452,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目(30370574)

摘　　要：目的探讨早期β受体阻断剂—美托洛尔治疗对大鼠急性心肌梗死(AMI)后心肌炎症因子和心功能的影响。方法结扎大鼠左前降支,建立AMI模型,存活者随机分为梗死对照组(MI组)和美托洛尔治疗组(MI B组),另设假手术组(S组)。MI B组参照中国心脏病研究(CCS2)方案给予4周美托洛尔治疗,MI组和S组仅以等体积生理盐水灌胃,观察4周后美托洛尔对心肌炎症和心功能的影响。结果与S组相比,MI组心肌组织中促炎性细胞因子TNFα、IL1β、IL6和抗炎性细胞因子IL10表达明显升高。与MI组比较,MI B组心肌细胞内TNFα和IL1β表达明显下降,IL10表达升高,而IL6和浸润心肌组织的淋巴细胞数差异无统计学意义。心脏超声显示MI B组左室功能明显改善。结论早期美托洛尔治疗AMI可以改善心肌炎症因子表达和心脏功能。美托洛尔有效改善心功能的作用机制至少部分与其降低心肌细胞促炎细胞因子和升高抗炎因子的免疫药理学作用有关。ObjectiveThe aim of study was to explore the effects of early β-adrenergic blockade-metoprolol treatment on myocardial inflammatory cytokine expression and heart function in rats after acute myocardial infarction (AMI). MethodsThe therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks (according to the protocol of CCS-2) were studied by the rat model of AMI. Myocardial inflammation was examined by taking account of the number of lymphocytes infiltrated in the myocardium and analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1β, 6 and tumor necrosis factor (TNF)-α and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. ResultsThe levels of TNF-α, IL-1β, IL-6 and ~IL-10 in AMI group were markedly elevated compared to sham rats (P<0.01) and the cytokines principally excreted by cardiac myocytes. After 4 weeks therapy, metoprolol reduced the production of TNF-α and IL-1β and increased IL-10 levels (P<0.05) in cardiac myocytes, but had no effect on the number of lymphocytes infiltrated in myocardium. Echocardiography showed that metoprolol markedly improved left heart function (P<0.05).ConclusionEarly metoprolol treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One immunopharmacologic mechanism underlying the beneficial effects of β-adrenergic blockade may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.

关 键 词：美托洛尔 炎症因子 心功能 大鼠心肌 早期 急性心肌梗死(AMI) IL-10 促炎性细胞因子 抗炎性细胞因子 TNF-α IL-1β Β受体阻断剂 促炎细胞因子 心肌组织 心脏病研究 心肌细胞内 淋巴细胞数 药理学作用 左前降支 生理盐水 

分 类 号：R542.22[医药卫生—心血管疾病]